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Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance. Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >–10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36. Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: −0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated. Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

PURPOSE To investigate the influence of age, gender, and underlying disease on the optical coherence tomography (OCT) features of choroidal neovascularization (CNV) secondary to inflammation, myopia (mCNV), and age-related macular degeneration (AMD-CNV). METHODS Demographic and clinical data of eyes with treatment-naive inflammatory CNV, mCNV, and Type 2 AMD-CNV were collected. Optical coherence tomography images were reviewed to determine the presence of pitchfork sign, pigment epithelial detachment, subretinal fluid (SRF), intraretinal cysts, subretinal hyperreflective material, atrophy, and outer retinal disruption graded 1 to 4. The influence of demographics and underlying etiology on OCT signs was investigated. RESULTS One hundred and eighty-five eyes from 179 patients were enrolled. The mean [SD] age was 36 [±14.4], 62 [±18], and 77 [±8] for the inflammatory CNV, mCNV, and AMD-CNV, respectively (P < 0.001). Multiple linear regression showed that the presence of pitchfork sign was negatively associated with age (P < 0.0001), regardless of underlying disease. By contrast, the SRF, pigment epithelial detachment, intraretinal cysts, and the outer retinal disruption were all positively influenced by age, regardless of gender and underlying disease (all P < 0.01). Logistic regression showed that none of the OCT signs increased the likelihood for diagnosis of inflammatory CNV. By contrast, the absence of SRF was suggestive for mCNVs, and the presence of pigment epithelial detachment and SRF was suggestive for AMD-CNVs. CONCLUSION The age of the patient had a significant effect on the OCT appearance of the CNV, particularly the presence of a pitchfork sign, regardless of the underlying etiology. The absence of SRF was suggestive for a diagnosis of mCNVs. The presence of SRF and pigment epithelial detachment was suggestive for AMD-CNVs.

To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a group of eyes with Type 1 and/or 2 MNV versus healthy eyes. In this cross-sectional, retrospective, multicenter, observational study, consecutive patients with Type 3 MNV, Type 1 and/or 2 MNV, and age-matched controls were included. PLEX Elite optical coherence tomography angiography was performed with a 6 × 6 mm scan pattern centered on the fovea. The CC FD was computed in 4 peripheral 1 × 1 mm squares to allow comparison between equidistant regions unaffected by MNV. Twenty Type 3, 20 Type 1 and/or 2 MNV [13 (65%) Type 1 MNV, 1 (5%) Type 2 MNV, and 6 (30%) mixed Type 1 and 2 MNV], and 20 age-matched controls were included. The mean impairment in the CC in the 4 peripheral squares was 16.07 ± 7.27% in Type 3 MNV eyes, 11.48 ± 5.59% in Type 1/2 MNV eyes, and 9.64 ± 3.59% in controls. Type 3 MNV displayed a statistically significantly higher CC FD compared with both Type 1/2 MNV (P = 0.031) and controls (P < 0.0001). No significant differences were observed between Type 1/2 MNV and controls (P = 0.223). CC FD was significantly greater in the peripheral macular regions of eyes with Type 3 MNV compared to eyes with Type 1/2 MNV and normal control eyes. Pathogenic choroidal mechanisms may differ in eyes with different MNV subtypes. Whereas focal CC impairment may drive the development of Type 1/2 MNV, diffuse CC disruption may be more important in eyes with Type 3 MNV.

To provide an image-based description of retinal features associated with risk for development of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD), as visualized with multimodal imaging anchored by structural OCT.Consensus meeting.International group that included those with expertise in imaging and AMD basic science and histology, and those with Reading Center experience in AMD clinical trials.As part of the Classification of Atrophy Meeting program, an international group of experts analyzed and discussed retinal multimodal imaging features in eyes with AMD associated with GA, risk of progression to GA, or both. Attendees undertook premeeting grading exercises that were reviewed during the meeting sessions. Meeting presentations illustrated established and investigational multimodal imaging features and associated histologic features. Each of these different features were then discussed openly by the entire group to arrive at consensus definitions. These definitions were applied to 40 additional images that were graded independently by attendees to refine the consensus definitions and descriptions further.Consensus was reached on images with descriptors for 12 features. These features included components of outer retinal atrophy (e.g., ellipsoid zone disruption), components of complete retinal pigment epithelium (RPE) and outer retinal atrophy (e.g., RPE perturbation with associated hypotransmission or hypertransmission), features frequently seen in eyes with atrophy (e.g., refractile drusen), and features conferring risk for atrophy development (e.g., hyperreflective foci, drusen, and subretinal drusenoid deposits).An international consensus on terms and descriptions was reached on multimodal imaging features associated GA and with risk for GA progression in eyes with AMD. We believe this information will be useful to clinicians who manage patients with AMD, researchers who study AMD disease interventions and pathogenesis, and those who design clinical trials for therapies targeting earlier AMD stages than GA expansion.

To analyze distribution and progression of multifocal choroiditis (MFC) inflammatory lesions and their correlations with clinical outcomes at 24 months.Distribution and progression of inflammatory lesions were evaluated in eyes with MFC using a semi-automatic approach based on fundus autofluorescence. Twenty-four-months clinical outcomes were correlated with baseline features.Twenty-five eyes from 20 patients were enrolled. Visual acuity (VA) significantly improved from baseline to 24 months. Chorioretinal lesions spared the fovea in most eyes. The area of inflammatory lesions at 24 months significantly increased. Final number and area of lesions were significantly influenced by baseline features. Inflammatory lesions enlarged over time regardless of MFC recurrences. New lesion and MFC relapses did not affect final outcomes.Final VA correlated with baseline VA. Scars resulting from MFC lesions enlarged overtime even when the disease was under control. New lesions and MFC relapses did not affect final outcomes.

Purpose The purpose of this study was to evaluate and compare the repeatability of optical coherence tomography angiography (OCTA) derived retinal vascular quantitative metrics using high resolution (HR) versus high speed (HS) acquisition modes. Methods Macular 4.4 × 2.9-mm OCTA images from normal, healthy volunteers were captured using both HR (768 A-scans × 256 B-scans) and HS (384 A-scans × 256 B-scans) acquisition protocols. Vessel density and vessel length density of the superficial capillary plexus and deep capillary plexus, as well as choriocapillaris flow deficit were computed. In a subset of eyes, the OCTA scans were repeated twice 2 days later and the same metrics were recomputed to assess repeatability, using intraclass correlation coefficients and coefficient of variation (CV). Results Comparison of measurements between HR and HS acquisitions in 41 healthy eyes showed statistically significant differences for all quantitative metrics (P < 0.01). However, no significant differences were observed among the three repeated scans (one on day 1 and two on day 3) obtained with each of the acquisition modes. The CVs ranged from 0.01 to 0.03 with the HR mode and 0.01 to 0.04 with the HS mode. The intraclass correlation coefficients (ICCs) among measurements were similar and high for both HR and HS modes, ranging from 0.844 to 0.949. Conclusions HR and HS OCTA acquisition modes both yielded repeatable quantitative metrics for the retinal circulation and the choriocapillaris. However, despite a similar field, the HR and HS derived measurements differed significantly. Translational Relevance To establish OCTA imaging in clinical and research practice, standardized and repeatability image analysis are necessary.

To describe a peculiar hyperreflective optical coherence tomography finding of nodular epiretinal gliosis at the fovea that may be a manifestation of Muller response to retinal injury. The central fovea is stabilized by the Muller cell cone but is at risk of foveal dehiscence due to various insults including vitreomacular traction which can lead to lamellar or full thickness macular hole formation. 1 Degenerative lamellar macular holes can be associated with epiretinal proliferation which has been attributed to activated Muller cells. 2 In this report, we describe a very unusual optical coherence tomography (OCT) finding of nodular epiretinal gliosis which may be the result of Muller cell activation and expansion.

Purpose Retinal vein cannulation is an experimental procedure during which a clot-dissolving drug is injected into an obstructed retinal vein. However, due to the fragility and minute size of retinal veins, such procedure is considered too risky to perform manually. With the aid of surgical robots, key limiting factors such as: unwanted eye rotations, hand tremor and instrument immobilization can be tackled. However, local instrument anatomy distance and force estimation remain unresolved issues. A reliable, real-time local interaction estimation between instrument tip and the retina could be a solution. This paper reports on the development of a combined force and distance sensing cannulation needle, and its experimental validation during in vivo animal trials. Methods Two prototypes are reported, relying on force and distance measurements based on FBG and OCT A-scan fibres, respectively. Both instruments provide an 80 μm needle tip and have outer shaft diameters of 0.6 and 2.3 mm, respectively. Results Both prototypes were characterized and experimentally validated ex vivo. Then, paired with a previously developed surgical robot, in vivo experimental validation was performed. The first prototype successfully demonstrated the feasibility of using a combined force and distance sensing instrument in an in vivo setting. Conclusion The results demonstrate the feasibility of deploying a combined sensing instrument in an in vivo setting. The performed study provides a foundation for further work on real-time local modelling of the surgical scene. This paper provides initial insights; however, additional processing remains necessary. ispartof: International Journal Of Computer Assisted Radiology And Surgery vol:14 issue:2 pages:301-309 ispartof: location:Germany status: published

To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD).Longitudinal study.We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe.The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis.Change in thickness of retinal layers and change in measures of vision.In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 ± 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 μm vs. 34.09 μm; P = 0.03). Low-luminance deficit was significantly worse at the final visit (P0.001) and correlated with PRL outer segment thickness (r = 0.33; P =0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 μm vs. 28.64 μm; P = 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs.The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD.

To investigate the utility of new wide-field optical coherence tomography (OCT) device in the evaluation of mid and far retinal periphery and to show its feasibility and advantages in clinical practice.Consecutive patients underwent a complete ophthalmologic examination including standard OCT and new prototype OCT2 derived from Heidelberg Spectralis.Thirty-one eyes of 31 patients were studied with a total of 44 lesions, including 18 retinal detachments, 15 retinal holes and tears, 9 retinoschisis, and 2 retinal tufts. Fourteen (32%) lesions were found in mid and 30 (68%) in far periphery with 9 (20%) lesions in the superior region, 10 (23%) in the superior temporal, 8 (18%) in the temporal, 4 (9%) in the inferior temporal, 7 (16%) in the inferior, 4 (9%) in the nasal, and 2 (5%) in the superior nasal. Among the lesions evaluated by OCT2, 10 (71%) in mid periphery and 11 (37%) in far periphery could be imaged by standard OCT.The introduction of OCT2 into clinical practice may provide significant benefits for imaging peripheral retinal disorders. The application of OCT2 technology with 55° lens and scan length and angle modulation could improve our understanding of peripheral vitreoretinal disorders and facilitate their management.

Background To compare fluorescein angiography (FA) and five different optical coherence tomography angiography (OCTA) devices and to test their reproducibility in the evaluation of retinal microaneurysms (MAs) secondary to diabetic retinopathy (DR). Methods On the same day, patients with DR were imaged with FA and five OCTA devices: prototype Spectralis OCTA, prototype PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton. For all OCTA devices, a 3×3 volume scan pattern was performed. MAs were evaluated for the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Results Twenty eyes of 15 patients with DR were included. FA counted a significantly higher number of MAs compared to OCTA devices. Spectralis OCTA obtained a significantly higher number of MAs compared to PlexElite, RTVue XR Avanti, AngioPlex and DRI OCT Triton (p Conclusions FA remains the best imaging modality to visualise retinal MAs. Spectralis OCTA was able to detect more MAs compared to other devices, likely due to the higher number of B-scans in the scanned area as well as due to the higher number of repeated B-scans. The high variability between OCTA devices should be taken into account for future clinical trials as in clinical practice.

The aim of this study is to describe the clinical presentation of vortex vein varices with multimodal imaging.The authors carried out a retrospective case series of eight patients (7 female, 1 male) with an average age of 60.2 years (min 8, max 84, median 68.5) presenting with vortex vein varices. All patients were evaluated at the Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy and at Luigi Sacco Hospital, University of Milan, Milan, Italy. Patients underwent complete ophthalmologic examinations, including best corrected visual acuity, intraocular pressure, anterior segment, and fundus examination. Imaging studies, including fundus color photography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain enhanced depth imaging optical coherence tomography were also performed. Ultra-widefield fluorescein angiography and ultra-widefield indocyanine angiography using the Heidelberg Retina Angiograph and the Staurenghi 230 SLO Retina Lens were used to demonstrate the disappearance of all retinal lesions when pressure was applied to the globe.All eight cases initially presented to the emergency room. One patient presented secondary to trauma, two patients presented for suspected hemangioma, whereas the other five were referred to the authors' hospitals for suspected retinal lesions. On examination, retinal abnormalities were identified in all 8 patients, with 7 (87.5%) oculus dexter and 1 (12.5%) oculus sinister, and with 1 (12.5%) inferotemporally, 3 (37.5%) superonasally, 3 (37.5%) inferonasally, and 1 (12.5%) inferiorly. Fundus color photography showed an elevated lesion in seven patients and a nonelevated red lesion in one patient. In all patients, near-infrared reflectance imaging showed a hyporeflective lesion in the periphery of the retina. Fundus autofluorescence identified round hypofluorescent rings surrounding weakly hyperfluorescent lesions in all patients. On fluorescein angiography, all lesions were initially hyperfluorescent with a hypofluorescent ring, with the lesion becoming hyperfluorescent after injection of dye. Indocyanine green angiography demonstrated dilation of the vortex vein ampullae in all patients. Spectral-domain enhanced depth imaging optical coherence tomography demonstrated dilated choroidal vessels and a hyporeflective cavity without subretinal fluid in all patients. Ultra-widefield fluorescein angiography and ultra-widefield indocyanine angiography demonstrated disappearance of all retinal lesions when pressure was applied to the globe. Findings are consistent with the diagnosis of vortex vein varix in all eight patients, with six patients (75%) exhibiting a single varix and two patients (25%) exhibiting a double varix.The diagnosis of vortex vein varices can be confirmed through clinical examination through the use of digital pressure to the globe during ophthalmoscopic examination. Adjunctive multimodal imaging (fundus color photography, near-infrared reflectance imaging, fundus autofluorescence, fluorescein angiography, indocyanine angiography, and spectral-domain enhanced depth imaging optical coherence tomography) was useful in the diagnosis of vortex vein varices in the authors' clinical cases. However, in more challenging clinical cases, the authors' novel use of the ultra-widefield contact lens for application of ocular pressure with a resulting resolution of the varix proved to be a useful and easy diagnostic imaging method for confirming the presence of vortex vein varices.

To evaluate the ability of optical coherence tomography angiography (OCTA) to detect macular neovascularization (MNV) in eyes with atrophy compared with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT).In this prospective study, eyes with MNV and atrophy (termed macular atrophy or MA) secondary to age-related macular degeneration (AMD), and AMD eyes with geographic atrophy (GA) without MNV underwent multimodal imaging with FA, ICGA, structural OCT, and OCTA. The presence of MNV was determined using all imaging modalities by senior retina specialists and was considered the gold standard reference. Each individual imaging modality was then evaluated independently by two expert readers for the presence of MNV in a masked fashion. Morphologic characteristics of the MNV were evaluated on the custom OCTA slab.Twenty-one patients with MA+MNV and 21 with GA only were enrolled. Manual segmentation on OCTA allowed detection of the MNV in 95.2% of eyes with MA+MNV and in 4.7% of eyes with GA, showing high specificity (95.2%) and sensitivity (95.2%). FA, ICGA, and OCT detected MNV in 57.1%, 52.3%, and 66.7% of eyes with MA+MNV and in 14.2%, 9.5%, and 42.8% with GA. Sensitivity and specificity were 85.7% and 57.1% for FA, 90.5% and 52.4% for ICGA, and 66.7% and 57.1% for OCT.OCTA appears to be superior to other imaging modalities for identification of MNV in eyes with macular atrophy. OCTA should be considered as part of the multimodal imaging evaluation of eyes with atrophy, particularly in the context of clinical trials.

Purpose: To evaluate safety and efficacy of the vascular endothelial growth factor binding protein abicipar pegol (abicipar) versus ranibizumab for neovascular age-related macular degeneration. Methods: Phase 2, multicenter, randomized, double-masked comparison (REACH study, stage 3). Patients (n = 64) received intravitreal injections of abicipar 1 mg or 2 mg at baseline, week 4, and week 8 (3 injections) or ranibizumab 0.5 mg at baseline and monthly (5 injections). Results: In the abicipar 1 mg (n = 25), abicipar 2 mg (n = 23), and ranibizumab (n = 16) arms, respectively, least-squares mean best-corrected visual acuity (BCVA) change from baseline was +6.2, +8.3, and +5.6 letters at week 16 (primary endpoint) and +8.2, +10.0, and +5.3 letters at week 20. Least-squares mean central retinal thickness (CRT) reduction from baseline was 134, 113, and 131 μm at week 16 and 116, 103, and 138 μm at week 20. Intraocular inflammation adverse events (AEs), reported in 5/48 (10.4%) abicipar-treated patients, resolved without sustained vision loss or other sequelae. Conclusions: Abicipar demonstrated durability of effect: BCVA and CRT improvements were similar between abicipar and ranibizumab at weeks 16 and 20 (8 and 12 weeks after the last abicipar injection and 4 weeks after the last ranibizumab injection). No serious AEs were reported.

Topic This study evaluated the cardiovascular/cerebrovascular safety profile of ranibizumab 0.5 mg versus sham ± verteporfin in patients with neovascular age-related macular degeneration (nAMD). In addition, comparisons of ranibizumab 0.3 mg with sham and ranibizumab 0.5 mg to 0.3 mg were performed. Clinical Relevance Intravitreal anti–vascular endothelial growth factor (VEGF) agents carry potential increased systemic risks, including cardiovascular or cerebrovascular events. Pooled safety analyses allow better interpretation of safety outcomes seen in individual clinical trials, especially for less common events. To our knowledge, this is the largest patient-level pooled analysis of patients with nAMD treated with ranibizumab. Methods Patient-level pooled analysis of data from 7 Genentech- and Novartis-sponsored phase II, III, and IV studies in nAMD that were completed by December 31, 2013. Pairwise comparisons (primary comparison: ranibizumab 0.5 mg [globally approved dose for nAMD] vs. sham or verteporfin) were performed using Cox proportional hazard regression (hazard ratios [HRs], 95% confidence intervals [CIs]) and rates per 100 patient-years. Standardized Medical Dictionary for Regulatory Activities queries (SMQs) and extended searches were used to identify relevant safety endpoints, including arterial thromboembolic events (ATEs), myocardial infarction (MI), stroke or transient ischemic attack (TIA), stroke (excluding TIA), vascular deaths, and major vascular events as defined by the Antiplatelet Trialists’ Collaboration (APTC). Results The HRs (95% CIs) for the primary comparison of ranibizumab 0.5 mg (n=480) versus sham or verteporfin (n=462) were 1.16 (0.72–1.88) for ATE, 1.33 (0.59–2.97) for MI, 1.43 (0.54–3.77) for stroke excluding TIA, 1.25 (0.61–2.55) for stroke or TIA, 0.57 (0.18–1.78) for vascular death, and 1.12 (0.64–1.98) for APTC events. Hazard ratio 95% CIs included 1, indicating no significant treatment differences, for all endpoints for comparison of ranibizumab 0.5 mg versus sham or verteporfin. Conclusions The rates of cardiovascular and cerebrovascular events were low in these patients with nAMD and not clinically meaningfully different for patients treated with ranibizumab 0.5 mg versus sham or verteporfin, which supports the favorable benefit–risk profile of ranibizumab in the patient population with nAMD. Pooling these studies allows an analysis with higher power and precision compared with individual study analyses.

Purpose To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. Design Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. Participants Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). Methods Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. Main Outcome Measures Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. Results Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 μm and 65.4±27.9 μm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. Conclusions Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.

Purpose: To describe the imaging features of choroidal neovascularization (CNV) associated with choroidal nevus using optical coherence tomography angiography (OCT-A) imaging. Methods: Retrospective observational case series. Patients with CNV secondary to choroidal nevus underwent full imaging examination including fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain OCT, and OCT-A. The OCT-A features were analyzed and correlated with conventional angiography findings and spectral domain OCT. Results: There were 11 eyes from 11 patients (6 men and 5 women, mean age of 65 ± 20.4 years) included in the analysis. Fluorescein angiography and indocyanine green angiography disclosed CNV in 90% and 83%, respectively. Optical coherence tomography angiography displayed CNV network in 11 eyes (100%) and the pattern was classified as “sea-fan” in 8 (73%) and “long filamentous linear vessels” in 3 (27%) eyes. Distinct from CNV, intrinsic vasculature within the nevus was observed in six eyes (55%), corresponding to those with chronic retinal pigment epithelium changes. Conclusion: Optical coherence tomography angiography is a useful imaging technique to disclose CNV associated with choroidal nevus. Despite the presence of intraretinal or subretinal fluid and hemorrhage, OCT-A revealed the CNV in all cases, results noninferior to indocyanine green angiography. This imaging modality can be useful for analysis of long-standing nevi with related exudation.

Background/aimsTo systematically compare the intermodality and inter-reader agreement for two blue-light confocal fundus autofluorescence (FAF) systems.MethodsThirty eyes (21 patients) with a diagnosis of geographic atrophy (GA) were enrolled. Eyes were imaged using two confocal blue-light FAF devices: (1) Spectralis device with a 488 nm excitation wavelength (488-FAF); (2) EIDON device with 450 nm excitation wavelength and the capability for ‘colour’ FAF imaging including both the individual red and green components of the emission spectrum. Furthermore, a third imaging modality (450-RF image) isolating and highlighting the red emission fluorescence component (REFC) was obtained and graded. Each image was graded by two readers to assess inter-reader variability and a single image for each modality was used to assess the intermodality variability.ResultsThe 95% coefficient of repeatability (1.35 mm2 for the 488-FAF-based grading, 8.13 mm2 for the 450-FAF-based grading and 1.08 mm2 for the 450-RF-based grading), the coefficient of variation (1.11 for 488-FAF, 2.05 for 450-FAF, 0.92 for 450-RF) and the intraclass correlation coefficient (0.994 for 488-FAF, 0.711 for 450-FAF, 0.997 for 450-RF) indicated that 450-FAF-based and 450-RF-based grading have the lowest and highest inter-reader agreements, respectively. The GA area was larger for 488-FAF images (median (IQR) 2.1 mm2 (0.8–6.4 mm2)) than for 450-FAF images (median (IQR) 1.0 mm2 (0.3–4.3 mm2); p2 (0.8–6.8 mm2); p=1.0).ConclusionThe isolation of the REFC from the 450-FAF images allowed for a reproducible quantification of GA. This assessment had good comparability with that obtained with 488-FAF images.

Purpose To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. Design A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. Participants One hundred seventy-eight eligible patients aged ≥18 years. Methods Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). Main Outcome Measures Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. Results Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. Conclusions The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12.

Optical coherence tomography (OCT) was one of the biggest advances in ophthalmic imaging. Building on that platform, OCT angiography (OCTA) provides depth resolved images of blood flow in the retina and choroid with levels of detail far exceeding that obtained with older forms of imaging. This new modality is challenging because of the need for new equipment and processing techniques, current limitations of imaging capability, and rapid advancements in both imaging and in our understanding of the imaging and applicable pathophysiology of the retina and choroid. These factors lead to a steep learning curve, even for those with a working understanding dye-based ocular angiography. All for a method of imaging that is a little more than 10 years old. This review begins with a historical account of the development of OCTA, and the methods used in OCTA, including signal processing, image generation, and display techniques. This forms the basis to understand what OCTA images show as well as how image artifacts arise. The anatomy and imaging of specific vascular layers of the eye are reviewed. The integration of OCTA in multimodal imaging in the evaluation of retinal vascular occlusive diseases, diabetic retinopathy, uveitis, inherited diseases, age-related macular degeneration, and disorders of the optic nerve is presented. OCTA is an exciting, disruptive technology. Its use is rapidly expanding in clinical practice as well as for research into the pathophysiology of diseases of the posterior pole.

To describe vitreal, retinal, and choroidal features of eyes affected by Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical coherence tomography (SD-OCT) and to evaluate their clinical impact.Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and uveitis tertiary referral centers were retrospectively evaluated. Spectral domain optical coherence tomography images were analyzed to evaluate the structural changes occurring in the vitreous, the retina, and the choroid in areas involved by ECE. Baseline and final best-corrected visual acuity were correlated with SD-OCT findings.Fifteen eyes from nine patients were enrolled. Vitreous involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15 eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes with vitreous involvement. Two patterns of retinal and choroidal findings were identified: the first (six eyes) confined within the inner retinal layers (Intraretinal Pattern), the second (nine eyes) involving both retina (full thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed both patterns. None of the eyes, regardless the pattern, showed choroidal thickening. Baseline best-corrected visual acuity was not associated with OCT pattern (P = 0.09). On the contrary, final best-corrected visual acuity was significantly higher in patients showing Intraretinal Pattern (∼20/25, 0.06 ± 0.08 LogMAR) than in subjects with Chorioretinal Pattern (∼20/50, 0.44 ± 0.30 LogMAR) (P = 0.01).Endogenous candida endophthalmitis showed peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement influencing the final best-corrected visual acuity were identified. Spectral domain optical coherence tomography could be useful in the diagnosis, management, and outcome prediction in ECE.

Purpose To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Design Consensus meeting. Participants Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. Methods As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. Main Outcome Measures A consensus classification system for atrophy and OCT-based criteria to identify atrophy. Results OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. Conclusions A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete representation of changes that occur in AMD than can be detected using color fundus photography alone. Longitudinal information is required to validate the implied risk of vision loss associated with these terms. This system will enable such future studies to be undertaken using consistent definitions.

To evaluate the clinical outcomes of vitrectomy with induction of posterior vitreous detachment for the treatment of optic disc pit maculopathy. We retrospectively evaluated medical records and imaging studies of 11 consecutive patients with optic disc pit maculopathy who underwent vitrectomy at Sacco University Hospital, Milan, Italy, between October 2008 and December 2015. Induction of a posterior vitreous detachment (PVD) was the aim of our surgery. Intravitreal injection of ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) was performed before surgery in three eyes of very young patients. Gas tamponade (sulfur hexafluoride (SF6) 20%) was used only in the first five cases. Main outcome measures were anatomic results as determined by optical coherence tomography and postoperative best-corrected visual acuity (BCVA). Before surgery, a macular detachment was present in 10 eyes and a lamellar hole of the outer retina was detected in 9 eyes. Intraoperatively, two iatrogenic paramacular holes developed in two patients during posterior hyaloid dissection. Time to PVD induction appeared to be greatly reduced in the three patients injected with ocriplasmin before surgery. Patients were followed up for a mean of 38 months (range, 18–84) after surgery. Postoperatively, one patient (9%) developed a retinal detachment that was repaired with one additional vitrectomy. Complete resolution of fluid in and under the fovea was achieved in 8 of the remaining 10 eyes (80%) without additional treatment. Reduction of the inner retinal fluid always preceded the decrease of outer retinal fluid, which in turn anticipated the absorption of macular detachment. The macular detachment resolved in a mean of 14 months after surgery. Postoperative BCVA (mean, 0.63) improved significantly compared with preoperative BCVA (mean, 0.27) (P = 0.005). Nine eyes (82%) had a postoperative BCVA of 0.5 or better. Vitrectomy with induction of PVD is a safe and successful therapeutic option for the treatment of optic disc pit maculopathy. The adjunct of ocriplasmin might facilitate the induction of PVD and reduce the risk of iatrogenic retinal holes.

Purpose To evaluate the reproducibility of parafoveal microvascular anatomy of 7 different optical coherence tomography angiography (OCT-A) devices by comparing vessel density (VD), fractal dimension (FD), and foveal avascular zone (FAZ) of superficial and deep capillary plexus in healthy volunteers. Design Reliability analysis. Methods Consecutive healthy volunteers presenting at the Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan in the same clinic visit were imaged by 7 different OCT-A devices: Optovue RTVue XR Avanti (Optovue, Inc, Fremont, California, USA), prototype Spectralis OCT-A (Spectralis; Heidelberg Engineering, Heidelberg, Germany), AngioPlex (Cirrus 5000 HD-OCT; Carl Zeiss Meditec, Inc, Dublin, California, USA), prototype PlexElite (Carl Zeiss Meditec), RS-3000 Advance (Nidek, Gamagori, Japan), OCT-HS100 (Canon, Tokyo, Japan), and Revo NX (Optopol Technology SA, Zawiercie, Poland). OCT-A examinations were performed using a 3 × 3 mm volume scan pattern centered on the fovea. Mean VD, FD, and FAZ values between the instruments were compared. Results The 7 different devices presented measurements with different mean values, with only a limited number of comparisons not significantly different between the instruments. Moreover, Bland-Altman analysis revealed that the limits of agreement for all the comparisons were not acceptable. Regression analysis was used in the development of tables to compare various devices, despite which large standard errors were found for both intercepts and slope conversion values. Conclusions Our results suggest that the comparison between instruments is nearly impossible and the set of measurements from the various instruments are not interchangeable regarding VD, FD, and FAZ for both the superficial and deep capillary plexus.

Purpose To evaluate the vitreal, retinal, and choroidal features using spectral domain optical coherence tomography (SD-OCT) in eyes affected by cytomegalovirus (CMV) retinitis. Methods Patients diagnosed with either active or inactive CMV retinitis were included in the study. Complete ophthalmic examination, serial color fundus photography, and SD-OCT (with and without enhanced depth imaging function) were performed for all the subjects at baseline and follow-up visits. The SD-OCT images were analyzed by two independent graders to evaluate the structural changes in areas of CMV retinitis. Prevalence data for vitreal, retinal, and choroidal SD-OCT features were collected. Results Twelve eyes from 9 patients (6 males, mean age: 52.7 ± 10.3 years) were enrolled. Nine eyes were diagnosed with active CMV retinitis at baseline. Active disease SD-OCT characteristic findings included nebulous vitritis (100%), posterior hyaloid thickening (83.3%), epiretinal membrane (100%), and retinal swelling (100%). Two distinct patterns of chorioretinal involvement were observed in active retinitis: 1) full-thickness retinitis (Full thickness retinitis) (n = 7 eyes) with choriocapillaris alterations and retinal pigment epithelial thickening and 2) cavernous retinitis (n = 3 eyes) characterized by inner retinal hyperreflectivity, large empty spaces in outer nuclear layer, and bridges of retinal tissue but retinal pigment epithelium and choriocapillaris sparing. Patients with cavernous retinitis develop retinal detachment during follow-up. Eyes with Full thickness retinitis developed choriocapillaris atrophy and choroidal thinning and retinal scars as the lesions healed. Conclusion There are two distinct patterns of chorioretinal involvement in CMV retinitis. SD-OCT is a useful tool in the diagnosis, management, and prediction of the outcome of CMV retinitis.

Purpose: Intraocular tuberculosis (IOTB) can be complicated by choroidal neovascularization (CNV). However, when the CNV development is not accompanied by clear signs of inflammation, the etiology can be missed, especially in countries nonendemic for tuberculosis. We describe the clinical and imaging features of CNVs presenting as the first sign of IOTB initially misdiagnosed as exudative age-related macular degeneration (AMD). Methods: A retrospective review of clinical and imaging data of patients initially misdiagnosed with neovascular AMD later diagnosed with inflammatory CNV secondary to IOTB at tertiary referral centers was conducted. Features of fundus photography, fluorescein angiography, indocyanine green angiography, and enhanced depth imaging optical coherence tomography were analyzed. Distinguishing features between neovascular AMD and IOTB-associated CNV were evaluated. Results: Five patients over 55 years of age, erroneously diagnosed with exudative AMD, were included in the study. Multimodal imaging analysis allowed identification of peculiar choroidal alterations such as choroidal granulomas or choroiditis suggestive for posterior uveitis. Systemic workup for granulomatous uveitis including immunologic investigations such as tuberculin skin test or QuantiFERON TB Gold® and radiologic investigations revealed tubercular etiology in all the cases, allowing correct diagnosis and management of the uveitis and related CNV. Conclusions: Choroidal neovascularization represents a rare and unusual presenting sign of IOTB that can be misleading especially when it occurs in the elderly living in countries with low prevalence of the disease. Multimodal imaging can be helpful and should be employed, especially in atypical cases of CNV, in order to avoid misdiagnosis and/or diagnostic delays.

Background/aimsTo evaluate intravitreal aflibercept versus laser in subgroups of patients with baseline Diabetic Retinopathy Severity Scale (DRSS) scores ≤43, 47, and ≥53 in VIVID-DME and VISTA-DME.MethodsPatients with diabetic macular oedema were randomised to receive intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after five initial monthly doses (2q8), or macular laser photocoagulation at baseline with sham injections at every visit. These post hoc analyses evaluate outcomes based on baseline DRSS scores in patients in the integrated dataset. The 2q4 and 2q8 treatment groups were also pooled.Results748 patients had a baseline DRSS score based on fundus photographs (≤43, n=301; 47, n=153; ≥53, n=294). At week 100, the least squares mean difference between treatment groups (effect of intravitreal aflibercept above that of laser, adjusting for baseline best-corrected visual acuity) was 8.9 (95% CI 5.99 to 11.81), 9.7 (95% CI 5.54 to 13.91), and 11.0 (95% CI 7.96 to 14.1) letters in those with baseline DRSS scores ≤43, 47, and ≥53, respectively. The proportions of patients with ≥2 step DRSS score improvement were greater in the intravitreal aflibercept group versus laser, respectively, for those with baseline DRSS scores of ≤43 (13% vs 5.9%), 47 (25.8% vs 4.5%), and ≥53 (64.5% vs 28.4%).ConclusionsRegardless of baseline DRSS score, functional outcomes were superior in intravitreal aflibercept-treated patients, demonstrating consistent treatment benefit across various baseline levels of retinopathy.Trial registration numbersNCT01331681 and NCT01363440, Post-results.

Purpose To demonstrate the efficacy and safety of once-daily nepafenac 0.3% ophthalmic suspension versus vehicle, based on clinical outcomes, after cataract surgery in patients with diabetes. Design Two prospective, randomized, multicenter, double-masked, vehicle-controlled phase 3 studies. Participants Total, 615 patients in study 1 and 605 patients in study 2. Methods Patients were randomized (1:1) to topical nepafenac 0.3% or vehicle once-daily starting the day before surgery and continuing for 90 days thereafter. Main Outcome Measures Key efficacy variables were: patients (%) in whom macular edema (ME) developed (≥30% increase from preoperative baseline central subfield macular thickness) within 90 days after cataract surgery and the patients (%) with a best-corrected visual acuity (BCVA) improvement of ≥15 letters from preoperative baseline through day 14 maintained through day 90. Secondary end points included: patients (%) with a BCVA improvement of ≥15 letters from preoperative baseline through days 90 and 60 and safety over 3 months. Results A significantly lower percentage of patients demonstrated ME within 90 days after surgery with nepafenac 0.3% versus vehicle (study 1: 2.3% vs. 17.3%; P P = 0.001; pooled: 4.1% vs. 15.9%; P P P = 0.671) in study 2, and 55.4% versus 46.7% ( P = 0.003) in the pooled analysis. A greater percentage of patients treated with nepafenac 0.3% versus vehicle in study 1 and similar percentage in study 2 had a BCVA improvement of ≥15 letters from preoperative baseline through day 90 (77.2% vs. 67.7% [ P = 0.009] and 65.4% vs. 65.9% [ P = 0.888]) and through day 60 (76.2% vs. 64.7% [ P = 0.002] and 68.9% vs. 62.1% [ P = 0.092]). No unanticipated adverse events were observed. Conclusions These studies demonstrated the clinical benefits of nepafenac 0.3% over vehicle in reducing the risk of postoperative ME, with the integrated analysis showing improved BCVA after cataract surgery in patients with diabetic retinopathy, with no unanticipated safety events.

PurposeTo report on progression of lamellar hole-associated epiretinal proliferation (LHEP) in eyes with lamellar macular holes (LMH) using spectral-domain optical coherence tomography (SD-OCT), and to correlate with intraretinal changes and visual function.MethodsFrom a retrospectively reviewed series of 167 eyes with non-full-thickness macular holes, we exclusively included a subgroup of 34 eyes with LMH and LHEP by SD-OCT evaluation. In these eyes, area of LHEP, intraretinal changes of defect diameter, central retinal thickness, defects of the ellipsoid zone and occurrence of a contractive epiretinal membrane were analysed. Additionally, clinical data were documented.ResultsArea of LHEP significantly increased during a mean follow-up period of 40.5 months (median 52 months). Analysing intraretinal changes, a significant enlargement of minimum and maximum horizontal lamellar hole diameter was found that correlated with the area of LHEP. Defects of the ellipsoid zone were seen in 65% of the eyes at baseline and in 85% at the end of follow-up. Increase of maximum horizontal hole diameter and ellipsoid zone defects correlated with a decline of visual acuity. Fifty per cent of patients with LMH and LHEP also demonstrated extrafoveal typical contractive epiretinal membranes with retinal folds.ConclusionsLong-term follow-up revealed an increase of the area of LHEP in eyes with LMH that correlated with the enlargement of lamellar hole diameter and ellipsoid zone defects. Our data delineate the progression of intraretinal changes in association with a decline of visual function in this subgroup of LMH eyes.

To evaluate macular changes in fellow eyes of patients diagnosed with lamellar macular hole (LMH) using spectral-domain optical coherence tomography (SD-OCT) and blue fundus autofluorescence (B-FAF). Fellow eyes of patients diagnosed with a LMH were retrospectively evaluated on OCT. Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were recorded. Corresponding B-FAF images, vitreo-macular relations, and type of epiretinal membranes (ERMs) were also examined. Thirty-five patients were included. At baseline, six fellow eyes (17%) showed a normal foveal profile, 26 (74%) had a tractional ERM, and three cases (9%) revealed a bilateral LMH, one of them with a lamellar hole-associated epiretinal proliferation (LHEP). A posterior vitreous detachment (PVD) was present in 29 patients (83%), four (11%) had only a vitreo-papillary adhesion (VPA), and two (6%) had both vitreo-macular adhesion (VMA) and VPA. After a mean follow-up of 4.6 ± 1.9 years, one eye (3%) developed a vitreous detachment from the macula with persistent VPA, and one developed a PVD from a VPA with subsequent ERM formation. BCVA and mean CFT remained stable in 35 eyes (100%). Likewise, no B-FAF signal variations were detected. One patient developed a LMH during the 3rd year of follow-up. Our data suggest that the presence of a LMH in one eye does not increase significantly the risk of developing the same condition in the fellow eye after 4 years. Bilateral condition is uncommon, and an ERM is often detected in the fellow eye. LHEPs were not observed in fellow eyes with foveal integrity, and all LHEPs observed (in main and fellow eyes) were always associated with LMHs; this supports the hypothesis that LHEP is a consequence and not a causative factor for LMHs. The occurrence of a LMH in one fellow eye after 3 years follow-up may suggest that a higher incidence of bilateral disease could develop in a longer time span.

PURPOSE: To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials. DESIGN: Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings. PARTICIPANTS: A panel of retina specialists. METHODS: During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held. MAIN OUTCOME MEASURES: Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials. RESULTS: Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions. CONCLUSIONS: A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.

During early months of Covid-19, significant nonattendance to scheduled appointments was noticed in our tertiary center for nAMD. This resulted in an increased rate of sub-macular hemorrhages in April 2020 compared to two control periods.

To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings.Evaluation of diagnostic test results.Panel of retina specialists.As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts.Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD.The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%.We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Background: Coronavirus disease 2019 (COVID-19) has been associated to microvascular alterations. We screened the fundus of patients with COVID-19 to detect alterations of the retina and its vasculature and to assess possible correlations with clinical parameters. Methods: Cross-sectional study. The presence of retinal alterations in patients with COVID-19 and subjects unexposed to the virus was assessed using fundus photographs and their prevalence was compared. Mean arteries diameter (MAD) and mean veins diameter (MVD) were compared between patients and unexposed subjects with multiple linear regression including age, sex, ethnicity, body mass index, smoking/alcohol consumption, hypertension, hyperlipidaemia, diabetes as covariates. The influence of clinical/lab parameters on retinal findings was tested in COVID-19 patients. Findings: 54 patients and 133 unexposed subjects were enrolled. Retinal findings in COVID-19 included: haemorrhages (9·25%), cotton wools spots (7·4%), dilated veins (27·7%), tortuous vessels (12·9%). Both MAD and MVD were higher in COVID-19 patients compared to unexposed subjects (98·3 ± 15·3 µm vs 91·9 ± 11·7 µm, p = 0.006 and 138·5 ± 21·5 µm vs 123·2 ± 13·0 µm, p

Background To evaluate the efficacy and safety of two individualized ranibizumab retreatment schemes in neovascular age-related macular degeneration. Methods Patients (N = 671) were randomized (1:1) to receive three initial monthly ranibizumab 0.5 mg injections, then retreatment guided by either best-corrected visual acuity (BCVA) loss (Group I) or BCVA loss and/or signs of disease activity on optical coherence tomography (OCT; Group II). The study was terminated prematurely and the decision to discontinue the study was made by the sponsor. Efficacy analyses were performed on patients who completed 12 months of the originally planned 24-month study. Safety analyses are presented for all safety analyzable patients. Results Of 671 randomized patients, 305 completed 12 months of the study. For the 12-month completers, baseline mean (standard deviation) BCVA and reading-center evaluated central subfield thickness (CSFT) were comparable [Group I: 60.9 (13.10) letters and 517.7(201.79) μm; Group II: 60.2 (12.21) letters and 515.3 (198.37) μm]. The change from baseline at Month 12 in BCVA was 6.7 (13.48) letters in Group I and 8.3 (13.53) letters in Group II and the change in CSFT was − 161.3 (163.48) μm and − 175.3 (170.45) μm, respectively. The mean number of ranibizumab injections was 8.2 in Group I and 8.4 in Group II. Conclusion Ranibizumab treatment resulted in visual and anatomic gains at 12 months for both retreatment strategies, with a trend in favor of OCT-guided vs BCVA loss guided retreatment. No new safety signals were seen. Trial registration www.ClinicalTrials.gov (NCT01780935). Registered 31 January 2013.

Background:The purpose of this study is to determine the prevalence of diabetes and diabetic macular edema in patients undergoing senile cataract surgery in Italy.Methods:It is a prospective, multicenter, cross-sectional study. Thirteen ophthalmic units equally distributed across the Italian territory have been involved in the study. For a period of 3 months, all subjects undergoing phacoemulsification received an Optical Coherence Tompgraphy (OCT) scan and were screened for the anamnestic presence of diabetes. In addition, five selected units collected blood samples from all their patients to measure glycated hemoglobin (HbA1c) levels and detect the presence of occult diabetes (HbA1c > 6.5%). In diabetic patients, levels of retinopathy were measured and diabetic macular edema was considered significant (clinically significant macular edema) when foveal thickness was above 30% of normal levels.Results:A total number of 3657 subjects have been screened. Among them, 20.4% were diabetics. Prevalence of diabetes was significantly higher in males (24.7%) than in females (17%). Levels of HbA1c were tested in a representative sample of 1216 consecutive subjects, and occult diabetes was diagnosed in 4.8% of cases. No significant differences were observed between age groups or different geographic areas. Among diabetic patients, diabetic macular edema of any kind was present in 27.5% (clinically significant macular edema (6.6%)). No significant differences were seen in the prevalence of diabetic macular edema between males and females or between age groups. Among the 745 diabetic patients, no signs of retinopathy were seen in 537 subjects (76.3%), while 101 patients (14.3%) had nonproliferative retinopathy, 13 (1.7%) had nontreated proliferative diabetic retinopathy, and 53 (7.5%) had laser-treated retinopathy. In the entire sample of 3657 subjects, a normal macula was present in 90.9% of cases, diabetic macular edema of any kind in 5.4%, and other maculopathies in 3.4%.Conclusion:In this large cohort study on patients undergoing cataract surgery, more than one-fourth were diabetics and more than one-fourth of these had diabetic macular edema. These high prevalences suggest the opportunity to plan an adequate preoperative assessment in all patients in order to reduce the risk of postoperative development or worsening of a sight-threatening complication such as chronic diabetic macular edema.

PURPOSE: To report a case of impending central retinal vein occlusion (iCRVO) in a COVID-19 patient. CASE REPORT: A 54 years old woman with COVID-19 related pneumonia presented to our emergency department complaining of scotomas and decreased vision in her right eye. Funduscopic examination and multimodal imaging revealed rare retinal hemorrhages, retinal whitening, and fern-like hypo-autofluorescent appearance typical of iCRVO. She had no risk factors other than a transient hyper-coagulability status likely related to the ongoing infection. Systemic treatment with steroids normalized her inflammatory and coagulation status and the occlusion completely resolved. CONCLUSIONS: Retinal circulation should be considered as a potential site for thromboembolic complications from COVID-19.

Wet age-related macular degeneration is a chronic condition culminating, in most cases, in blindness. The introduction of anti-angiogenic agents in 2006 has represented a major breakthrough in the treatment of the disease, but timely and effective treatment with regular follow-up and monitoring is mandatory to stabilize and preserve visual acuity. In clinical practice, however, appropriate therapy provision is frequently challenged by economic and organizational issues that result in suboptimal visual outcomes and increased incidence of legal blindness. International Guidelines have defined a diagnostic and therapeutic pathway to ensure the best practice in wet age-related macular degeneration management, but reference parameters to evaluate and compare the performance of Retina Centers are lacking. To address the appropriateness of wet age-related macular degeneration management in Italy, a multidisciplinary panel of ten experts gathered in three meetings. They defined three sets of indicators and relative benchmark values that each Center should comply with to ensure patients optimal care already from the first access: (a) clinical intervention indicators, to determine the possible Center’s deviation from the diagnostic and therapeutic pathway; (b) outcome indicator, to evaluate the socioeconomic impact of the healthcare systems’ performance; (c) management indicators, to test the size of the gap between the Center’s supply and demand. Once the indicators have been analyzed, healthcare systems can plan actions to improve appropriateness and monitor their effects. However, to put this in practice, a concerted effort by all parts involved in healthcare provision is required, together with adequate systems to analyze clinical and administrative documentation.

To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (TE) or a pro re nata (PRN) regimen over 4 years in a real-world setting.Four-year, multicenter, retrospective comparative study.Two hundred sixty-four patients with treatment-naive nAMD.Consecutive patients with nAMD received anti-VEGF therapy according to a TE (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios.Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections.At baseline, MA was present in 24% and 20% of study eyes in TE and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the TE and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the TE and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between TE and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692).Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a TE regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

To investigate the pathogenesis of Multiple Evanescent White Dot Syndrome (MEWDS) using multimodal imaging (MMI).Retrospective case series of 7 patients with acute MEWDS. Each patient underwent: near-infrared reflectance (IR), blue and near-infrared autofluorescence (FAF and NIRAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), enhanced depth imaging optical coherence tomography (EDI-OCT) on Spectralis, and optical coherence tomography angiography on OCTA Spectralis, XR Avanti or Plex Elite 9000.OCTA and FA findings of early hyperfluorescence depict an unaffected choriocapillaris. On ICGA early to late hypofluorescent lesions corresponded to the hyporeflectivity on IR, consistent with altered reflectivity of the RPE. The SDI-OCT showed ellipsoid zone disruption as confirmed by FAF hyperautofluorescence. Some lesions showed a hypertransmission sign underneath the RPE, possibly due to changes in RPE intracellular melanin as suggested by NIRAF hypoautofluorescence.The MMI findings of MEWDS are secondary to RPE reflectivity changes, suggesting its pivotal role.

To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data.Consensus meeting.An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists.During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components.A consensus classification of neovascular AMD.The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated.The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

The advent of optical coherence tomography (OCT) revolutionized both clinical assessment and research of vitreoretinal conditions. Since then, extraordinary advances have been made in this imaging technology, including the relatively recent development of swept-source OCT (SS-OCT). SS-OCT enables a fast scan rate and utilizes a tunable swept laser, thus enabling the incorporation of longer wavelengths than conventional spectral-domain devices. These features enable imaging of larger areas with reduced motion artifact, and a better visualization of the choroidal vasculature, respectively. Building on the principles of OCT, swept-source OCT has also been applied to OCT angiography (SS-OCTA), thus enabling a non-invasive in depth-resolved imaging of the retinal and choroidal microvasculature. Despite their advantages, the widespread use of SS-OCT and SS-OCTA remains relatively limited. In this review, we summarize the technical details, advantages and limitations of SS-OCT and SS-OCTA, with a particular emphasis on their relevance for the study of retinal conditions. Additionally, we comprehensively review relevant studies performed to date to the study of retinal health and disease, and highlight current gaps in knowledge and opportunities to take advantage of swept source technology to improve our current understanding of many medical and surgical chorioretinal conditions. We anticipate that SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift to more widespread adoption of new imaging technology to clinical practice.

Background:Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders1. HCQ modulates immune response through several mechanisms and has a tropism for pigmented ocular tissues, particularly retinal pigment epithelium (RPE)2. Its accumulation within RPE cells can lead to sight threatening retinal toxicity, with bull’s eye maculopathy (BEM) representing its advanced phenotype. 3 Quantitative Auto-Fluorescence (qAF) is an imaging modality that allows the measurement of retinal auto-fluorescence following short-wavelength light (488nm) excitation of retinal fluorophores (lipofuscin). 4 Two recent studies have focused on qAF values in patients treated with HCQ 5,6. In both cases qAF was increased in eyes with BEM. Furthermore, Reichel et al.6 were able to detect increased values of qAF in patients without BEM as early as 6 months after the start of HCQ treatment using an experimental imaging analysis procedure.Objectives:To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Methods:Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight (ABW) and/or renal insufficiency)7 but no alterations on Spectral Domain - Optical Coherence Tomography, Short-Wavelength Autofluorescence and 10-2 Visual Field examination were recruited. Healthy subject matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analyzed using the conventional qAF grid by Delori calculating the qAF of 8 sectors of the intermediate ring and the mean of those values (qAF8).Results:Thirty-nine patients treated with HCQ (38 females, mean age 52,1 ± 8,6 years) and 39 untreated subjects (38 females, mean age 51,2 ± 8,6 years). In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF8 compared to untreated subjects (294,7 ±65,3 vs 268,9 ± 57,5), the difference was not significant (p=0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared to untreated subjects (all pFigure 1.Visual representation of a model predicting the standardized qAF values as influenced by age and HCQ daily dose/ABW, calculated for a treatment duration of 15 years.Conclusion:These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure. Further studies are required to improve our understanding of preclinical stages of HCQ retinopathy and the possible role of qAF in the HCQ toxicity screening.References:[1]Haładyj, E., Sikora, M., Felis-Giemza, A. & Olesińska, M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia56, 164–173 (2018).[2]Rosenthal, A. R., Kolb, H., Bergsma, D., Huxsoll, D. & Hopkins, J. L. Chloroquine retinopathy in the rhesus monkey. Invest. Ophthalmol. Vis. Sci.17, 1158–1175 (1978).[3]Modi, Y. S. & Singh, R. P. Bull’s-Eye Maculopathy Associated with Hydroxychloroquine. N. Engl. J. Med.380, 1656 (2019).[4]Sparrow, J. R., Duncker, T., Schuerch, K., Paavo, M. & de Carvalho, J. R. L. J. Lessons learned from quantitative fundus autofluorescence. Prog. Retin. Eye Res.74, 100774 (2020).[5]Greenstein, V. C. et al. Quantitative Fundus Autofluorescence in HCQ Retinopathy. Invest. Ophthalmol. Vis. Sci.61, 41 (2020).[6]Reichel, C. et al. Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy. Transl. Vis. Sci. Technol.9, 42 (2020).[7]Yusuf, I. H., Sharma, S., Luqmani, R. & Downes, S. M. Hydroxychloroquine retinopathy. Eye (Lond).31, 828–845 (2017).Disclosure of Interests:Salvatore Parrulli: None declared, Mariano Cozzi Grant/research support from: Bayer, Nidek, Zeiss, Matteo Airaldi: None declared, Francesco Romano: None declared, Francesco Viola: None declared, Piercarlo Sarzi-Puttini: None declared, Giovanni Staurenghi Grant/research support from: Heidelberg Engineering (C), QuantelMedical (C), Centervue (C), Carl Zeiss Meditec (C), Alcon (C), Allergan (C), Bayer (C), Boheringer (C), Genentech (C), GSK (C),Novartis (C), and Roche (C), Optos (F), Optovue (F) and Centervue (F), Alessandro Invernizzi Grant/research support from: Novartis (C), Bayer (C)

To assess the ability of enhanced depth imaging optical coherence tomography (EDI-OCT) in detecting variations in the structure and size of choroidal granulomas in response to treatment and to compare these findings with indocyanine green angiography (ICGA).EDI-OCT and ICGA images of choroidal granulomas in eyes of patients diagnosed with tubercular or sarcoid uveitis were obtained at baseline and follow-up visits. Two independent masked observers analyzed the lesions to compare changes in their structural features such as shape, reflectivity, and margins, among others, through time. The size of each lesion was manually measured on EDI-OCT and ICGA images at all the visits. In addition, longitudinal assessment of choroidal area was performed on the EDI-OCT images during the course of follow-up.Twenty-eight granulomas (16 tubercular and 12 sarcoid; 7 patients) were included in the study. Using EDI-OCT, significant decrease in the mean size of lesions could be appreciated after 1 month of treatment (0.29 mm at baseline vs. 0.18 mm at 1 month; P0.001). However, ICGA did not reveal significant decrease in lesion size at 1 month compared with baseline (0.94 vs. 0.76 mm; P = 0.07). The granulomas followed a characteristic healing pattern in which the antero-posterior extent (depth) decreased first, followed by decrease in their lateral extent. Apart from size, the choroidal granulomas did not show significant changes in their morphological features on EDI-OCT with treatment.EDI-OCT may be more sensitive than ICGA in detecting early variations in the size of choroidal granulomas. Morphometric analyses of choroidal granulomas on EDI-OCT may be very useful in monitoring the response to treatment in patients with choroidal granulomas.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

There is a lack of agreement regarding the types of lesions and clinical conditions that should be included in the term "geographic atrophy." Varied and conflicting views prevail throughout the literature and are currently used by retinal experts and other health care professionals.We reviewed the nominal definition of the term "geographic atrophy" and conducted a search of the ophthalmologic literature focusing on preceding terminologies and the first citations of the term "geographic atrophy" secondary to age-related macular degeneration.According to the nominal definition, the term "geography" stands for a detailed description of the surface features of a specific region, indicating its relative position. However, it does not necessarily imply that the borders of the region must be sharply demarcated or related to any anatomical structures. The term "geographical areas of atrophy" was initially cited in the 1960s in the ophthalmologic literature in the context of uveitic eye disease and shortly thereafter also for the description of variants of "senile macular degeneration." However, no direct explanation could be found in the literature as to why the terms "geographical" and "geographic" were chosen. Presumably the terms were used as the atrophic regions resembled the map of a continent or well-defined country borders on thematic geographical maps. With the evolution of the terminology, the commonly used adjunct "of the retinal pigment epithelium" was frequently omitted and solely the term "geographic atrophy" prevailed for the nonexudative late-stage of age-related macular degeneration itself. Along with the quantification of atrophic areas, based on different imaging modalities and the use of both manual and semiautomated approaches, various and inconsistent definitions for the minimal lesion diameter or size of atrophic lesions have also emerged.Reconsideration of the application of the term "geographic atrophy" in the context of age-related macular degeneration seems to be prudent given ongoing advances in multimodal retinal imaging technology with identification of various phenotypic characteristics, and the observation of atrophy development in eyes under antiangiogenic therapy.

PurposeTo determine whether reticular pseudodrusen (RPD) confer a long-term increased risk of progression to late age-related macular degeneration (AMD) in the fellow eye of patients with unilateral wet-AMD.Patients and methodsThis was a multicenter, combined prospective and retrospective, longitudinal, observational, study. Patients with wet-AMD in one eye were recruited from two centers and evaluated on the risk of progression to late-AMD in the second eye (study eye). A minimum follow-up of 5 years was required, unless progression occurred first. Baseline retinal profile of patients was evaluated using multimodal imaging. Baseline images were graded by two separate centers.ResultsWe recruited 88 patients (48 female) with a mean age of 75.6±7.1 years and mean follow-up of 65.7±20.9 months. Baseline prevalence of RPD was 58% (n=51). There was no statistically significant association of RPD with increased age (P=0.29) or sex distribution (P=0.39). The most sensitive image modality for RPD was IR (93%), followed by FAF (92%), OCT (74%, RF (33%) and CFP (29%). After 5 years, 54.50% (n=48) of the study eyes progressed to late-AMD. Of those, 81.25% (n=39) developed CNV and 18.75% (n=9) geographic atrophy. After correcting for age and sex, the presence of RPD was significantly associated with development of late-stage AMD (OR=2.55, P=0.03).ConclusionA multimodal approach is mandatory for RPD detection. RPD are highly prevalent in the fellow eyes of patients with unilateral neovascular AMD. Presence of RPD is associated with increased long-term risk of progression, highlighting the importance of comprehensive multimodal retinal imaging and careful monitoring of at-risk patients.

To summarize the recent literature describing the application of modern technologies in the study of patients with geographic atrophy (GA) secondary to age-related macular degeneration.Review of the literature describing the terms and definitions used to describe GA, imaging modalities used to capture and measure GA, and the tests of visual function and functional deficits that occur in patients with GA.In this paper, we describe the evolution of the definitions used to describe GA. We compare imaging modalities used in the characterization of GA, report on the sensitivity and specificity of the techniques where data exist, and describe the correlations between these various modes of capturing the presence of GA. We review the functional tests that have been used in patients with GA, and critically examine their ability to detect and quantify visual deficits.Ophthalmologists and retina specialists now have a wide range of assessments available for the functional and anatomic characterization of GA in patients with age-related macular degeneration. To date, studies have been limited by their unimodal approach, and we recommend that future studies of GA use multimodal imaging. We also suggest strategies for the optimal functional testing of patients with GA.